2934 h/ICDONALD .AND TABOR
The Journal of Organic Chemistry
Molecular Rearrangements.
VI.’ A Study of the Rearrangements
of 2-Chlorobicyclo[2.2.l]hept-2-ene exo-Oxide RICHARD N. MCDONALD AND THEODORE E. TABOR^ Department of Chemistry, Kansas State University, Manhattan, Kansas 66601 Received January 13, 1968 The synthesis of 2-chlorobicyclo[2.2.1]hept-2-ene ezo-oxide ( 2 ) is reported. Neat, thermal rearrangement of 2 gives rise to two major products, em-3-chlorobicyclo [2.2.1]heptan-2-one (3, 37.4%) and ezo-2-chlorobicyclo[2.2.l]hepta.n-7-one (4, 34.9%), in addition to seven minor products. Acetolysis of 2 gives a ratio of 4/3 of 2.7 along with a,cetoxy ketone product resulting from the addition of acetic acid to 2. Reaction of 2 with anhydrous hydrogen chloride in ether leads to the unexpected addition product 3,3-dichlorobicyclo[2.2.1]heptan-em-2-01, Possible mechanistic pathways for these reactions are considered.
Our previous work in the rearrangements of l-chlorocis- and -trans-4-methylcyclohexene oxide led us to conclude that an a-ketocarbonium ion-chloride ion pair was produced as a common intermediate which yields trans-2-chloro-4-met hylcyclohexanone exclusively. To expand our knowledge of the rearrangements of achloro epoxides and, hopefully, substantiate further the ion pair intermediacy, we initiated an investigation into the synthesis and rearrangements of 2-chlorobicyclo[2.2.1]lhept-Zene em-oxide (2). It was felt that 2 served experimental purposes well for at least two reasons: (1) the rearrangements would be starting with a single epoxide rather than. a mixture, and (2) the literature holds a wealth of information on the carbonium ion chemistry of this bicyclic ~ y s t e m . ~ 2-Chlorobicyclo [2.2.1Ihept-2-ene (1) was prepared by the Diels-Alder reaction of cyclopentadiene and trans-l,2-dichloroethylene, hydr~genation,~and the product dehydrochlorinated in good yield with potassium t-butoxide in t-butyl alcohol.6 Epoxidation of 1 gave 2 in 65% yield. The assignment of the ex0 configuration to the epoxide is based upon the analogous epoxidation of bicyclo [2.2.1Ihept-2-ene6 and the observation that the nuclear magnetic resonance (nmr) spectrum of the epoxide shows a one-proton doublet at high field (7 9.18) for the anti-7 hydrogen.’ A slow, neat>,thermal rearrangement of the a-chloro epoxide 2 was conducted in a manner analogous to the thermal rearrangement of 1-chloro-4-methylcyclohexene 0xide.l Analysis of the rearrangement mixture by gas chromatography (gc) with integration of the areas under the peaks showed two major components in addition to 11% (of unrearranged epoxide and seven minor components. The two major components of the rearrangement were identified as exo-3-chlorobicyclo[2.2.1lheptan-2-one (3, 37.4%) and ezo-Zchlorobicyclo [2.2.1]heptan-7-one (4, 34.9%). Several minor products were as follows : endo-3-chlorobicyclo [2.2.1](1) For paper V In this series, see R. N. McDonald and T. E. Tabor, J. Amer. Chem. SOC.,89, 6573 (1967). (2) NDEA Fellow, 1962-1965. This represents a portion of a dissertation presented by R. E. Tabor to t h e Graduate School of Kansas State University in partial fulfillment, of the requirements for the Ph.D. Degree. (3) Some recent reviews on this subject are (a) P. D. Bartlett, “Nonclassical Ions,” W. A. Benjamin, Inc., New York, N. Y., 1965;(b) G.D.Sargent, Quart. Rev. (London). 40,301 (1966);(c) J. A. Berson, “Molecular Rearrangements,” Vol. 1. P. de Mayo, Ed., Interscience Publishers, Ino., New York, N. Y., 1963,p 111. (4) J. D.Roberts, F. 0. Johnson, and R. 4.Carboni, J . Amer. Chem. Soc.,
76, 5692 (1954). (5) N. A. LeBel, i b i d . , 82, 623 (1960). (6) H.KNart and T. Takeshita, J . Ore. Chem., IS, 670 (1963). (7) K. Tori, K. Kitahonoki, Y. Takano, H. Tanida, and T. Tsuji [Tetrahedron Lett., 559 (1964)]report this proton appears as a doublet a t r 9.30 in bioyclo I2.2.1 Ihept-2-ene em-oxide.
heptan-Zone (5, 4.3%), a saturated alcohol whose nmr spectrum suggests the structure 3,3-dichlorobicyclo [2.2.1]heptan-ezo-2-01 (6, 2.9%), a liquid unsaturated alcohol which from its infrared and nmr spectra is believed to be 1-chlorobicyclo [2.2.1Ihept-2-ensyn-7-01 (7, 2.7%), l13-cyclohexadiene (8, 3.0%), and carbon monoxide (1.6%). The other two minor components (2.0% of total) were not identified. 0
\
H
2
4
3
\
c1
5
6
7
8
Diene 8 and carbon monoxide were found to be arising from the thermal decomposition (during the gc analysis) of bicyclo 12.2.1Ihept-2-en-7-one (9) present in the rearrangement mixture. The photolytic cleavage of 9 to give 8 and carbon monoxide has been reported.8 The isomeric chloro ketones 3 and 5 were identified by their gc retention times, and by collection and comparison of their infrared spectra with authentic samples. The exo isomer 3 was prepared independently by sulfuryl chloride chlorination of bicyclo [2.2.l]heptan-2one. The endo isomer 5 was then obtained by base equilibration of the ex0 isomer.9 No report on the preparation of the chloro ketone 4 could be found in the literature. Walborsky and Loncrini’O have reported that the major product upon treat(8) D. 1. Shuster, F.-T. Lee, A. Padwa, and P. G. Gassman, J. Org. Chem., 80,2262 (1965). (9) (a) J. Meinwald, Y. C. Meinwald, and T. N. Baker, J . Amer. Chem. Soc., 86,4074 (1964);(b) E.Tobler. D. E. Battin, and D. J. Foster, J. Org. Chem., 29, 2834 (1964). (10) H.M.Walborskyand D. F. Loncrini, ibid., 24, 1117 (1957).
MOLECULAR REARRANGEMENTS 2935
Vol. $3, No. 7 : July 1968 ment of bicyclo [2.2.1Ihept-2-ene exo-oxide (10) with 48% hydrobromic acid is exo-2-bromobicyclo [2.2.1]heptan-syn-7-01 ( l l a ) . I n the present study it was found that treatment of 10 with concentrated hydrochloric acid gave the corresponding chloro alcohol, exo2-chlorobicyclo [2.2.1Iheptan-syn-7-01 ( l l b ) . The prop-
10
Xla, X-
possibility that the oxidation product was 3,3-dichlorobicyclo [2,2.1 ]heptan-2-one. Hydrolysis of the dichloroalcohol with aqueous lithium carbonate gave 1-chlorobicyclo [2.2.1jheptaneexo-2,syn-7-diol (12). Diol 12 would be the expected hydrolysis product from either 1-exo-2-dichlorobicyclo [2.2.1]heptan-syn-7-01 (13)16 or 6 , with the latter involving Wagner-Meerwein rearrangement.
Br
b,X==CI
erties of l l b differed from those of exo- and endo3-chlorobic yclo [a.2.1 Iheptan-exo-2-01,gb endo-3-chlorobicyclo [2.2.1]heptan-endo-2-01,~~ and syn- and anti7-chlorobicyclo [2.2.11Iheptan-em-2-01.~ The infrared and nmr spectra were in agreement with the structure 1lb.I’ Oxidation of the chloro alcohol l l b with chromium trioxide in acetic acid gave the desired chloro ketone 4. This oxidation product was identical with the chloro ketone formed in 34.9% yield in the thermal rearrangement of 2. The infrared spectrum of 4 showed carbonyl absorptions at 5.43 (m) and 5.62 (s) p which are quite characteristic of bicyclo [2.2.1Jheptan-7-0nes.’~ In the nmr spectrum of 4 the enclo-2 hydrogen appeared as a multiplet at, T 5.25 (1 H). This oxidation product also gave further support for the 7 position of the hydroxyl group in 1115. Additional evidence for the 7keto structure of 4 was afforded by conversion into its ethylene ketal, dehydrochlorination, and hydrolysis to the known bicyclo [2.2.l]hept-2-en-7-one (9).12,13 Gc analysis of 9 gave 1,3-~yclohexadiene( 8 ) and carbon monoxide. The combined data for the solid dichloro alcohol, assigned structure 6 , obtained as a minor product (2.9%) in the rearrangement of chloro epoxide 2 initially made a structural assignment somewhat perplexing. The alcohol was found to correspond to the molecular formula C7HloC120 as determined by its molecular weight and elemental analysis. This indicated that the alcohol was arising by addition of a molecule of hydrogen chloride to the a-chloro epoxide 2. It was subsequently found that the dichloro alcohol was the major product (27.1%) when 2 was treated with hydrogen chloride in ether. When the dichloro alcohol was oxidized with chromium trioxide in acetic acid, a solid ketone was obtained whose infrared spectrum showed carbonyl absorptions a t 5.48 (m) and 5.62 (s) p. These absorptions suggested that this ketone was a bicyclo[2.2.1 ]heptan-7-one, in view of the similar absorptions observed for ex0-2chlorobicyclo 12.2.1Iheptan-7-one (4). However, Krieger14 has reported that the carbonyl absorption of 3,3-dibromobicyclo [2.2.1Iheptan-2-one appears at 1772 cm-l (5.64 p ) compared to 1761 (5.68 p ) and 1758 em-’ (5.69 p ) for endo- and exo-3-bromobicyclo[2.2.1]heptan-2-one1 respectively. This then allowed for the (11) The nmr spectral asslgnments agree with those of the acetate of l l b reported by W.C. Baird [J‘. Org. Chem., 81, 2411 (1966)l. (12) P. G. Gassman and P. G. Pape, zbtd., 19, 160 (1964). (13) R. K . Bly and R. S. My, zbzd., OS, 3165 (1963). (14) H. Krieger, Svomen Kemzstzlehtt, S l B , 112 (1958); Chem. Abstr., 68, 13423e (1958).
12
OH /
13
The nmr spectrum allows a differentiation between 6 and 13. In the latter structure two carbon-bound downfield protons should be observed since chlorine and hydroxyl have similar effective shielding constants;16 only one is observed. The spectrum (CCL, TMS internal standard) can be reasonably interpreted in terms of structure 6 with the endo-C:n proton as a singlet a t T 6.17 (indication of some splitting), the hydroxyl proton as a broad singlet a t r 6.83 (concentration dependent), the bridgehead C4 proton as broad adsorption a t 7.26,’’ and the bridgehead C1 proton as a broad singlet at T 7.77, which is not completely separated from the complex absorption from r 7.8 to 9.0 for the six methylene protons. The liquid unsaturated alcohol obtained as a minor product (2.7%) in the rearrangement of 2 was assigned the structure of 1-chlorobicyclo [2.2.1Ihept-2-en-syn7-01 (7) on the basis of its nmr spectrum. The complex absorption centered a t ca. r 4.0 was assigned to the two vinyl protons. The anti-7 proton appeared as a singlet a t r 6.29 and the hydroxyl proton appeared as a singlet a t 7.10 (concentration dependent). The broad singlet a t r 7.23 was assigned to the lone bridgehead proton and the remaining four methylene protons gave rise to complex absorption in the region of r 7.9-9.3. The assignments agree quite well with those reported for bicyclo[2.2.1]hept-2-en-syn-7-01.~8 As was mentioned previously, the dichloro alcohol 6 was the major product (27.1%) when the a-chloro epoxide 2 was treated with hydrogen chloride in ether. This reaction also gave rise to the chloro ketones 3 and 4 in 13.0 and 23.2% yields, respectively. Four other products (32.8% total) remain unidentified. Another component observed in the gc analysis of the reaction mixture integrated as 3.9%, and was indicated by its retention time to be unreacted epoxide. endo-3-Chloro(15) Reference 1 1 describes the analogous hydrolysis of ezo-2-chloro-syn-7acetoxybicyclo (2.2.1]heptane to bicyclo (2.2.1 lheptan~ezo-2,syn-7-diol. (16) L. M. Jackman, “Applications of Nuclear Magnetic Resonance Spectroscopy in Organic Chemistry,” Pergamon Press, Inc., New York, N . Y., 1959, p 59. (17) The fact that this proton absorption is at lower field than is normally observed for bicyclo[2.2.llheptanes (ca. I 7.8) is explained as due t o the deshielding effect of the two chlorines on C3. (18) R. R. Sauers and R. M. Hawthorne, J . 0 7 0 . Chem., 19, 1685 (1964).
The Journal of Organic Chemistry
2936 MCDONALD AND TABOR bicyclo [2.2.1]heptan.-2-one (5) was indicated to be present in only a trace amount. The reaction of a-chloro epoxide 2 with anhydrous acetic acid was carried out by the dropwise addition of 2 to a relatively large volume of acetic acid in order to determine whether any acetoxy ketone products as well as chloro ketone products would be formed. Gc analysis of the crude product of this reaction showed the presence of a t least 14 products. The major product of the reaction was found to be a hydroxyacetate whose structure is indicated to be 1-chloro-exo-2-acetoxybicyclo [2.2.l]heptan-s,yn-7-01 (14, 24.5% by integra-
15
14
0
H 16
tion). Other products of this reaction are given in Table I. I n addition, t,here were seven other minor components (lS.3% total) which were unidentified, except that one of these (1.7%) was indicated by its retention time to be unreacted epoxide. TABLE I Compound
% yield
l-Chloro-ero-2-syn-7-diacetoxybicyclo [2.2.1]heptane (15 ) 14 ezo-2-Acetoxybicyclo[2.2.1] heptan-7-one (16) 12.6 ero-2-Chlorobicyclo[2.2.1] heptan-7-one (4) 13.3 5.0 ezo-3-Chlorobicyclo[2.2.l]heptan-2-one (3) endo-3-Chlorobicyclo[2.2.1]heptan-2-one ( 5 ) 3.5 3,3-Dichlorobicyclo [2.2.1]heptan-em-2-01 ( 6 ) 8.9
Compounds 3-6 were identified by their retention times and by collection of each component from the gas chrorqatogram and comparison of their infrared spectra with those of known samples. The acetoxy ketone 16 was collected from the gas chromatogram and identified by comparison of its infrared spectrum with that of a known ~amp1e.l~ The major product of the acetolysis, 14, was collected from the gas chromatogram. The elemental analysis and molecular weight were in agreement with the formula C9H13C103. Its structural assignment as 14 is based on the interpretation of its nmr spectra and conversion into a known compound. The placement of the acetoxyl group at C-2 is argued from mechanistic considerations. The diacetate 15 likewise was collected from the gas chromatogram and could also be prepared by acetylation of 14. Attempted reduction of 14 with lithium aluminum hydride gave only recovered starting material probably due to the initial formation of an insoluble alkoxide (19) The infrared spectra of 16 and the endo isomer were kindly furnished by Professor P. G. Gassman.
intermediate. Reduction of the diacetate 15 with lithium aluminum hydride proceeded readily a t room temperature to yield 1-chlorobicyclo [2.2.1lheptaneezo-2, syn-7-diol (12). No ketal formation was realized by treating 12 with acetone and p-toluenesulfonic acid in benzene. However, using the ketal exchange method by reaction of 12 with 2,2-dimethoxypropane and ptoluenesulfonic acid catalyst in benzene gave a small amount of material believed to be the cyclic ketal in addition to considerable recovered diol. Both the infrared and nmr spectra indicated the presence of the geminal dimethyl group in this product. Molecular models indicate that there are considerable steric interactions involved in the ketal, which might explain the difficulties in its preparation and its apparent ease of cleavage during purification attempts. The indication that the ketal could be formed, however, was added support for the exo-syn relationship of the hydroxyl groups in the diol 12. To establish completely the structure of the diol as 12, it was first treated with sodium in refluxing glyme followed by reaction with dimethyl sulfate. Three major products were isolated from this reaction mixture and all were dimethyl ethers. The mass and nmr spectral data and mechanistic considerations suggest that these products are l-chloro-exo-2,syn-7-dimethoxybicyclo[2.2.l]heptane (33%), exo-2,syn-7-dimethoxybicyclo [2.2.l]heptane (17, 20%), and l-methyl-exo2, syn-7-dimethoxybicyclo [2.2.1]heptane (43%). Compound 17 was identified by comparison of its infrared spectrum with that of a known sample prepared by a similar treatment of bicyclo [2.2.1]heptane-exo-2,syn7-diol.2o Although neither exo-3-acetoxybicyclo [2.2.1Iheptan2-one nor its endo isomer was isolated from the acetolysis of a-chloro epoxide 2, the presence of these compounds could not be excluded since seven minor products of this reaction were not isolated and identified. Several unsuccessful attempts were made to prepare these compoundsS2
Discussion The formation of products in the rearrangements of a-chloro epoxide 2 can be interpreted by the two different set's of processes shown in Scheme I. No data are available to allow one to say if and where equilibrating classical carbonium ions or their nonclassical counterparts are involved in these pathways. Some criticism of the process on the right-hand half of Scheme I can be offered. It does not involve chlorine as the migrating group to form a-chloro ketone product, which is contrary to our previous finding1V2land those of others,22and requires a 3,2-endo hydride shift to produce exo-3-chlorobicyclo [2.2.l Iheptan-Zone. A rebuttal to the first part of this criticism might be that the bicyclo [2.2.l]heptane system is so prone to Wagner-Rleerwein rearrangemenk that this takes precedence over the normal processes found in acyclic and alicyclic a-chloro epoxides. The C1, or C4--5u (20) K. Alder, F. H. Flock, and H. Wirtz, Chem. Ber., 91, 609 (1958). (21) (a) R. N. McDonald and P. A. Schwab, J . Amer. Chem. Soc., 86, 4004 (1963); (b) J . Ore. Chem., 29, 2459 (1964). (22) A. Kirrman. P. Duhamel, and R. Nouri-Bimorghi, Bull. Sac. Chim. Fr., 3264 (1964); Ann., 691, 33 (1966); R. Nouri-Bimorghi, C. R. Acad. Sci. (Paris). Ser. C, 262, 759 (1966); G. A. Razuvaev, V. S. Etlis, and N . N. Trofirnov, Zh. Ore. Khim., 1, 2128 (1964) [Chem. Abstr.. 64, 11145e (1966)l.
MOLECULAR REARRANGEMENTS 2937
VoE. 33, No. 7, July 1968 orbitals appear from models to be spatially well arranged in 2 for participation in C-0 bond fissions as has been argued for bicyclo [2.2.1lhept-ezo-2-yl tosylate. Such an argument, however, should also lead to the conclusion that the rearrangements of 2 and bicyclo[2.2.1 Iheptene mo-oxide should occur with similar facility. This is obviouisly not the case when the present work is compared with that of Crandall.23 The second part of the criticism is possibly the more serious since most reactions which could involve 3,2e d o shifts of hydrogen or other atoms or groups take alternate paths in this bicyclic ring system.24 Such a 3,2-endo migration appears as an attractive possibility for the formation of bicyclo [2.2.l]heptan-2-one as a major product during attempted gc purification of bicyclo[2.2.l]heptene e x o - o ~ i d e . ~No ~ proof of such a process has, however, been offered. The yield of ezo-3-chlorobicyclo[2.2.1Iheptan-Zone is somewhat larger than that of exo-2-chlorobicyclo[2.2.l]heptan-7-one and much greater than that of any products formed by 6,2-hydride shift (not established as even present) in the neat thermal rearrangement of 2. This would then mean that the rate of endo-3,2 hydride shift is essentially equal to that of WagnerMeerwein rearrangement and far greater than that of 6,Zhydride shift. This is exceedingly difficult to accept in light of the nmr study of the norbornyl cation by Saunders, Schleyer, and Olah258 in mixed SbFhS02-S02F2solvent who calculated that a t -120" the 3,2-hydride shift is slower than 6,Zhydride shift and Wagner-Meerwein rearrangement by a minimum of 108.8. Berson and ooworkers25b have found that the exo-3-methylbicyclo 12.2.lIhept-2-yl cation does not undergo the endo-3,2 hydride shift despite the large thermodynamic driving force for such a process. However, such an endo-3,2 hydride shift has recently been established in the pinacol rearrangement of endo-3phenyl-2,3-exo,cis-bornanediol .26,27 The authors believe that a concerted endo-3,2 hydride shift with epoxide ring opening is ruled out from strain and stereoelectronic considerations just as a concerted l12-chlorine shift was argued unreasonable in certain other a-chloro epoxide rearrangements2'&and would not account for the stereospecificity in product formation in the neat thermal rearrangement of 1chloro-cis- and -6rans4methylcyclohexene oxide.' (23) J. K. Crandall, J . O w . Chem., 49, 2830 (1964). (24) D. C. Kleinfelter and T. E. Dye, J . Amer. Chem. SOC.,$6, 3174 (1966). (25) (a) M.Saunders, P. von R. Schleyer, and G.A. Olah. ibid., 86, 5680 (1964);(b) J. A. Berson, J. H. Hammom, A. W. McRowe, R. G. Bergman, A. Remanick, and D.Houston, ibid., 89, 2590 (1967). (26) A. W. Bushel1 and P. wilder, %bid.,89, 5721 (1967). (27) Referees have suggested that S may be formed by endo capture of chloride b y the a-ketocarbonium ion, or possibly by an endo-2,3chloride shift from i, followed by acid-caLalyzed isomerization. That this does not occur
i
CI
is shown by the fact that 6 is almost completely uneffected when placed in a rearrangement o f t , as well as b y itself or in the presence of hydrogen chloride when placed in sealed tubes at 5 mm of pressure and heated in a bath at SOo for the same length of time RS a rearrangement: R. N. Steppel, unpublished results. A maximum of about 2% of S might be produced by this route. I t is also interesting to note that the same products in about the same distribution are produced on "go analysis" of 4 with the injection port at 250";some unrssrranged P is evident under these conditions.
The significant difference between the right and left hand sides of Scheme I is that each side yields a different enantiomer of em-3-chlorobicyclo [2.2.1lheptan-2one if optically active a-chloro epoxide 2 is used. Such studies are presently underway and should allow us to determine the extent to which both ( 2 2 - 0 and Cs-0 bond fissions occur.
Experimental Section28 truns-5,6-Dichlorobicyclo[2.2.1]hept-2-eae.-The Diels-Alder adduct from cyclopentadiene and trans-1 ,Z-dichloroethylene was obtained in 67% yield: bp 80.0-76.6' (17.0-14.5 mm); n% 1.5123 ( k 4 34%, bp 76-78' (18 mm), 71%D 1.5101). truns-2,3-Dichlorobicyclo[2.2.1]heptane.-Hydrogenation of trans-5.6-dichlorobicyclo 12.2.11hept-2-ene according to the published procedure,' except using palladium on carbon rather than platinum oxide as the catalyst, gave truns-2,3-dichlorobicyclo[2.2.l]heptane in 96% yield: bp 85" (17.5 mm), n% 1.5040 (lit.4 85% yield, bp 85-86' (18 mm), n% 1.5015). 2-Chlorobicyclo[2.2.1]hept-2-ene (l).-Dehydrochlorin~tion of truns-2,3-dichlorobicyclo[2.2.1] heptane was carried out using the procedure of LeBel6 with potassium t-butoxide in t-butyl alcohol. 2-Chlorobicyclo[2.2.1] hept-2-ene was obtained in 60% yield: bp 69.5-71.5" (67.5-68.0 mm), TPD1.4896 (lit.4 bp 64-66' (52 mm), n % ~1.4880). 2-Chlorobicyclo[2.2.1]hept-2-ene ezo-Oxide (2).-A solution of 40.0 g (0.311 mol) of 2-chlorobicyclo[2.2.~]hept-2-ene in 25 ml of methylene chloride was treated with a solution of 72.0 g of mchloroperbemoic acid (82% minimum purity) in 700 ml of methylene chloride for 10 hr. After work-up, vacuum distillation through a short path column gave 34.9 g (77.7%) of crude epoxide containing a small amount of methylene chloride. Redistillation (semimicro spinning-band column) gave 29.4 g (65.4%) of pure 2-chlorobicyclof2.2.1J hept-2-ene em-oxide: ~ The epoxide could be bp 52.2-53.4' (5.1-5.2 mm), n e 61.4886. stored under Dry Ice for periods of several weeks with little or no rearrangement, but samples left a t room temperature and atmospheric pressure soon underwent a violent exothermic rearrangement with evolution of hydrogen chloride fumes. Elemental analysis was not attempted because of this facile decomposition. A strong band a t 11.54 M was observed in the infrared spectrum and is believed to be due to the epoxide ring vibration. The nmr spectrum (CCt, TMS internal standard) exhibited absorptions at T 6.86 (singlet, 1, epoxide ring), 7.38 (multiplet, 1, bridgehead C,), 7.53 (multiplet, 1, bridgehead C4), 8.2-8.9 (multiplet, 5, Cs, Ca, and syn-C,), and 9.18 (broad doublet, 1, unti-C?). Neat Thermal Rearrangement of 2-Chlorobicyclo[2.2.1]hept2-ene ezo-Oxide.-A 4.1-g sample of epoxide 2 w&s placed in a 10 ml distillation flask connected to a semimicro spinning-band column and brought to reflux a t reduced pressure, bp 51.0' (4.9 mm), with a wax bath maintained at 80'. These conditions are essentially those used for distillation of the epoxide in which only slight rearrangement occurred over a period of several hours. After heating for 46 hr the sample was still refluxing at 51.0' (4.9 mm). -4t the end of 187.5 hr the head temperature had decremed to 39.5' (4.9 mm) and refluxing had slowed considerably. After a total of 260.5 hr refluxing had completely ceased and the head temperature had dropped to 30.0" (4.9 mm). At this point heating was discontinued, and the flask was cooled, removed, and stored under Dry Ice. During the rearrangment the sample had slowly dificolored and by the end of the rearrangement had become dark red. About 60% of the mixture is volatile, the remaining 40% being polymeric material. The infrared spectrum of the rearrangement mixture showed intense carbonyl absorption a t 5.63, weak carbonyl absorption at 5.41 and weak hydroxyl absorption a t 2.87 p . Also, a weak epoxide absorption at 11.52 p indicated that the rearrangement still had not proceeded to completion. (28) All melting points were taken on a Kofler hot stage and are corrected. Boiling points are uncorrected. Infrared spectra were determined on a P.E Model 137 or 237 spectrophotometer; nmr spectra were determined on a Varian A-60 spectrometer, and mass spectra were determined with a Bendix timeof-flight mass spectrometer. Molecular weights were obtained either mass spectrometrically or with an osmometer, Model 301A. Go analyses were performed using an F t M Model 500 gas chromatograph. Microanaiyaea were performed by Galbraith Laboratories, Inc., Knoxville, Tenn.
2938 R'ICDONALD AND TABOR
The Journal of Organic Chemistry
SCHEME I POSSIBLE MECHANISTIC PATHWAYS FOR THE REARRANQEMENTS OF 2
68
R \
I.
A
0
-HCt
c1W*M
/
9
A
A
H
Cl
-
/
3,2 Hshift
A
H
a?
1
t
&
\A-
H
A
A
&
Gc analysis of the volatile portion of the rearrangement mixture using a 0.25 in. X 6 ft 20% Carbowax 20M on 60/80 Chromosorb W column a t 200" showed the presence of ten major components. The peak numbers, retention times, and integrated percentages were as follows: no. 1, 0.23 min, 1.6Tc; no. 2, 0.41 min, 3.0%; no. 3, 1.70 min, 1.2%; no. 4, 2.04 min, l l . O ~ c r no. 5, 3.15 min, 0.870; no. 6, 4.20 min, 2.7%; no. 7, 4.80 min, 37.4%; no. 8, 5.66 min, 34.9%; no. 9, 6.16 min, 4.3%; and no. 10, 9.68 min, 2.9%. Peak no. 4 was indicated to be unrearranged epoxide by comparison of retention times and also by the fact that this peak had essentially disappeared after the rearranged sample had been standing for several weeks. The component could not be collected for identification as the epoxide, because the epoxide was found to undergo rearrangement in the detector block under these conditions. Peaks no. 7 and 9 had retention times corresponding to exoand endo-3-chlorobicyclo [2.2.1]heptan-2-one, respectively. Collection of each of these components from the gc and comparison of the infrared spectra with authentic samples confirmed the assignments. Collection of peak no. 8 from the gc followed by infrared analysis showed this component to be identical with eso-2-chlorobicyclo [22.11heptan-7Ione prepared independently by the oxidation of ezo-2-chlorobicyclo[2.2.1] heptan-syn-7-01. When collections were attempted on peak no. 1, it was found that no material would condense in the Dry Ice-isopropyl alcohol cooled receiver. Peak no. 2 was obtained as a volatile, colorless liquid whose nmr spectrum was found to be identical with that of an authentic sample of 1,3-cyclohexadiene. This suggested that peak no. 1might be carbon monoxide. When investigated, peak no. 1 did give a positive test for carbon monoxide using a U. S. Safety Service Co., No. CO-100 indicating tube for SAFCO-METER carbon monoxide indicator.
CI
U T -A
A
The infrared spectrum of a low boiling fraction obtained by distillation of another sample of the rearrangement mixture strongly indicated the presence of bicyclo[2.2.1] hept-2-en-7-one by the intense carbonyl absorption at 5.62, a medium intense carbonyl absorption a t 5.42, a weak carbon-carbon double bond absorption at 6.18, and vinyl hydrogen absorption a t 3.23 (w) and 14.27 fi (s), in good agreement with the report, of Bly and Bly.l* A 2,4-dinitrophenylhydrazone recrystallized twice from 95% ethanol, melted a t 136.0-137.5' (lit.l2 mp 136-137'). When the sample containing this ketone was subjected to gc analysis under the conditions employed above, two components were observed at the same retention times as peaks no. 1 and 2 in the rearrangement mixture and were identified as carbon monoxide and 1,3-cyclohexadiene. Collection of peak no. 10 from the gc gave a white crystalline solid, which melted a t 104-107' after vacuum sublimation. An osmometric molecular weight in ethanol gave a value of 182.8, which indicated the addition of a molecule of hydrogen chloride to the epoxide. The structure of this solid is assigned as 3,3dichlorobicyclo [2.2.1] heptan-ezo-2-01. Anal. Calcd for C7HloC120: C, 46.44; H, 5.77; mol wt, 181.06. Found: C, 46.75; H, 5.60. Peak no. 6 was collected a8 a clear, colorless liquid and assigned the structure of l-chlorobicyclo[2.2.1] hept-2-en-syn-7-01 on the basis of its spectral data and mechanistic considerations. Insufficient quantities of peaks no. 3 and 5 were obtained for determination of their structures. exo-3-Chlorobicyclo[2.2.I] heptan-2-one (3).-A 25.0-g (0.227 mol) sample of bicyclo[2.2.l]heptan-2-onewas placed in a I W m l , three-necked flask equipped with a condenser, an addition funnel, and a magnetic stirrer. The flask was heated until all of the solid ketone melted, and then 30.7 g (0.227 mol) of sulfuryl chloride was added dropwise. A vigorous gas evolution ensued, and heating was continued until the evolution ceased. After
Vol. $8,N o . 7, July 1968
MOLECULAR REARRANGEMENTS 2939
The nmr spectrum (neat, TMS external standard) exhibited cooling, the light yellow reaction mixture weighed 34.8 g. absorptions at 7 5.25 (multiplet, 1, endo-Cz) and 6.8-8.3 (comGc analysis using a 0.25 in. X 6 ft 20% Carbowax 20M on 60/80 plex, 8). Chromosorb W column a t 225' showed the presence of six peaks. This ketone gave a 2,4-dinitrophenylhydrazonewhich melted The yield of 3 was 77%. Distillation (semimicro spinning-band a t 140.0-142.0". column) gave pure ezo-3-chlorobicyclo[2.2.1] heptan-2-one: bp ero-Z-Chlorobicyclo[Z.Z. 11heptan-7-one Ethylene Ketal.-The 85.3' (4.8 mm); n% 1.4976 (lit.98 bp 88-89" (4.5 mm), n 2 * . 6 ~ procedure of Meinwald, Meinwald, and Baker% was employed, 1.4941). The infrared and nmr spectra were in agreement with using ethylene glycol, benzene solvent, and p-toluenesulfonic those r e p ~ r t e d . ~ acid catalyst. A 0.805-g (5.57 mmol) sample of ezo-2-chloroendo-3-Chlorobicyclo[2.2.1] heptan-2-one (5).-A mixture of 6.02 g (0.0417 mol) of ezo-3-chlorobicyclo[2.2.l]heptan-2-one, bicyclo[2.2.l]heptan-7-one gave 0.778 g of the crude ketal after distillation through a short path column. The yield of the 12.0 g of potassium carbonate, and 50 ml of water was heated ketal based on gc integration was 63.5%. under reflux for 20 hr. After cooling, the reaction mixture was Bicyclo[Z 2.11 hept-2-en-7-one Ethylene Ketal .-To a refluxing extracted continuously with ether overnight. The ether extract solution of potassium t-butoxide in t-butyl alcohol, prepared from was dried and the ether was removed under reduced pressure leaving 5.5 g of a light brown liquid residue. Gc analysis using 0.675 g (0.173 g-atom) of potassium and 10 ml of dry t-butyl alcohol, was added a solution of 0.778 g (85.7% pure, 3.54 mmol) a 0.2.5 in. x 6 ft 20% Carbowax 20h2 on 60/80 Chromosorb W of ero-2-chlorobicyclo[2.2.1]heptan-7-one ethylene ketal in 10 column a t 225" showed two major components which were ml of dry t-butyl alcohol. The reaction mixture immediately identified as ezo-3-chlorobicyclo[2.2.1] heptan-2-one (40.8%) and began to turn cloudy and after refluxing for an additional 28 hr endo-3-chlorobicyclo[2.2.1] heptan-2-one (59.2%), respectively. a white solid had precipitated. The reaction mixture was cooled, Gc collections gave the cndo isomer as a waxy solid, mp 55.5added to 50 ml of water, and extracted continuously with ether 60.5' (lit. mp 53-56",9%lit. mp 50-53' gb). The infrared and overnight. After drying, the ether solution was concentrated nmr spectra were in agreement with the reported d a h g by distillation at atmospheric pressure, leaving 1.26 g of a light Bicyclo[2.2.l]hept-Z-eneezo-Oxide (lo).-A solution of 25.0 g yellow liquid residue. Gc collection of the product gave 0.408 g (0.265 mol) of bicyclo[:2.2.l]hept-2-enein 25 ml of methylene (76%). The nmr spectrum (neat, TMS external standard) chloride was treated with a solution of 61.3 g of m-chloroperexhibited absorptions a t 7 3.48 (triplet, 2, vinyl), 5.78 (multiplet, benzoic acid (82Yc minimum purity) in 650 ml of methylene 4, dioxolane), 7.13 (quintet, 2, bridgeheads), 7.66 (multiplet, 2, chloride for 8 hr. After work-up, vacuum distillat.ion through a eso-Cs and eso-Cs), and 8.65 (multiplet, 2, endo-Cs and endo-C6). short path column gave 21.2 g (72.6%) of crude epoxide as a Bicyclo[Z.2.l]hept-2-en-7-one(9).-A 0.400-g (0.00263 mol) white crystalline solid. After recrystallization twice for hexane, sample of bicyclo[2.2.1] hept-2-en-7-one ethylene ketal was the epoxide showed m.p 139-142" in a sealed capillary (lit.ag hydrolyzed with 5% sulfuric acid according to the method of mp 125.5-126.5"). Gassman and Pape.12 After work-up, there ww obtained eso-2-Chlorobicyclo[2.2.1] heptan-syn-7-01 (llb).-This com0.550 g of a clear, colorless liquid containing some solvent pound was prepared in I% manner quite similar t,o that described (pentane). The infrared spectrum of this crude product was in by Walborsky and Loncrini'o for the preparation of ezo-2-bromoagreement with that for bicycl0[2.2.1] hept-Z-en-7bicyclo[2.2.1] heptan-syn-7-01, To 50 ml of concentrated one, showing carbonyl absorptions at 5.36 (m) and 5.60 (s), hydrochloric acid cooled to below 10" was added 12.96 g (0.117 carbon double bond absorption at 6.17 (w), and vinyl carbon mol) of bicyclo[2.2.l]hept-2-eneezo-oxide at such a rate that hydrogen absorptions at 3.28 (w) and 14.27 ,u (s). the temperature did not rise above 15". The mixture was allowed Gc analysis using a 0.25 in. X 7.5 ft 20% Carbowax 20M to stir for an additional. 1 hr with cooling and then was added column at 100" showed decomposition of the ketone to give carbon to 100 ml of water. The aqueons mixture was extracted with monoxide and 1,3-cyclohexadiene. The ketone could be confour 5O-ml portions of ether, and the combined ether extracts verted into its 2,4-dinitrophenylhydrazone,which melted a t were washed with 25 ml of 10% sodium carbonate solution and 138.5-139.2" (lit.12mp 136-137'). 25 ml of water, and dried. Removal of the ether under reduced Reaction of 2-Chlorobicyclo[2 2.11hept-2-ene ero-Oxide with pressure gave 12.6 g of n light yellow liquid residue. Gc analysis Hydrogen Chloride in Ether .-Anhydrous hydrogen chloride gas using a 0.25 in. x 6 ft 20% Carbowax 20M on 60/80 Chromosorb was bubbled through 25 ml of anhydrous ether at room temperaW column a t 190" showed the presence of threepeaks. The cent,er ture for ca. 15 min. A solution of 2.067 g (0.0143 mol) of 2peak (50.77,) was collected as a white crystalline solid, which chlorobicyclo [2.2.1]hept-2-ene eso-oxide in 10 ml of anhydrous after recrystallization frmom hexane had mp 52.2-53.2'. ether was added slowly and the mixture allowed to stir at room Anal. Calcd for CiII1lCIO: C, 57.34; H, 7.56. Found: C, temperature for 3.5 hr. The solution was then concentrated 57.45; H, 7.72. under reduced pressure to give 2.293 g of a clear, colorless liquid In the infrared spectrum the hydroxyl group exhibited strong which developed a light pink color upon standing. absorption a t 3.07 ,u, while in the nmr spectrum (CCla, TMS Gc analysis using a 0.25 in. X 6 f t 20% Carbowax 20M on internal standard) absa'rptions occurred a t 7 6.0 (complex, 2, 60/80 Chromosorb W column at 200" showed the presence of endo-Ct and anti-Ci), 7,.07 (singlet, 1, hydroxyl), 7.8 (complex, eight major components. The retention times and integrated 4, bridgeheads and C3), and 8.0-9.1 (complex, 4, Ca and (26). percentages were as follows: peak no. 1, 1.71 min, 3.97,; eso-2-Chlorobicyclo[2.2.l]heptan-7-one (4).-To a solution of peak no. 2, 3.35 min, 7.9%; peak no. 3, 3.60 min, 3.2%; 0.860 g (5.87 mniol) of ezo-2-chlorobicyclo[2.2.1]heptan-syn-7-01 peak no. 4, 3.90 min, 13.07,; peak no. 5, 4.59 min, 23.2%; in 4 ml of glacial acetic acid n'as added slowly a solution of 0.464 peak no. 6, 4.98 min, 12.4%; peak no. 7, 7.54 min, 27.1%; and g (4.6 mmol) of chromium trioxide in 12 ml of glacial acetic acid. peak no. 8, 13.27 min, 9.3%. The exothermic reaction was moderated with a water bath at room temperature. After stirring a t room temperature for 2 Peak no. 1 was indicated to be unreacted epoxide by its retenhr, the reaction mixture was added to 20 ml of water, followed tion time only. Peaks no. 2 and 3 were not identified. Peak no. by extraction with four :!O-ml portions of pentane. The combined heptan-%one (3) 4 was identified as eso-3-chlorobicyclo[2.2.1] pentane ext,ractswere washed with 10 ml of 10% sodium carbonate by its retention time. Peak no. 5 was identified as eso-2-chlorosolution, 10 ml of water, and dried. Removal of the pentane bicyclo[2.2.l]heptan-7-one (4) by its retention time and by under reduced pressure left a light yellow liquid residue. The collection and comparison of its infrared spectrum with that of infrared spectrum of the crude product showed carbonyl absorpan authentic sample. The retention time of peak no. 6 suggested tions at 5.44 (m), 5.64 (s), and 5.77 (s) p . A medium intense it to be endo-3-chlorobicyclo[2.2.1]heptan-2-one ( 5 ) , but after hydroxyl absorption at 2.94 p indicated the presence of some collection of this component the infrared spectrum showed only starting material. Column chromatography using Woelm a weak, sharp carbonyl absorption at 5.66 and a strong hydroxyl acid-washed alumina, activity grade 1, gave a clear liquid, absorption at 2.90 p. Thus, this peak from the gc is an unknown eluted with methylene chloride, which showed carbonyl absorpcompound probably containing a small amount of 5 . tions at 5.43 (m) and 5.62 (s) p , but no hydroxyl absorption. Peak no. 7 was identified as 3,3-dichlorobicyclo[2.2.1]heptanPurification by gc collections using a 0.25 in. X 6 f t 20% eso-2-01 ( 6 ) by its retention time and by collection and comparison Carbowax 20M on 60/80 Chromosorb W column a t 176" gave of its infrared spectrum with that of the same material obtained pure ezo-2-chlorobicyclo[2.2.1]heptan-7-one in low yield. in the thermal rearrangement of the epoxide. A collected sample, Anal. Calcd for C7MgClO: C, 58.14; H, 6.27. Found: C, after vacuum sublimation and recrystallization from hexane, 58.09; H, 6.40. melted a t 103.0-109.0" (sealed capillary). The melting points of samples of this alcohol appeared to vary somewhat depending upon length of exposure to the atmosphere. (29) S. U. Soloway and S. J. Cristol, J . Org. Chem., '26, 327 (1960).
2940 MCDONALD .AND TABOR Collection of peak no. 8 gave a tan waxy solid. Vacuum sublimation of the collected material gave a white waxy solid, which melted at 85-92". This material was not identified, but the infrared spectrum showed major absorptions at 2.98 ( s ) , 5.73 (m), and 6.15 (w) p . Reaction of 3.3-Dichlorobicvclo72 2.11heptan-ezo-2-01 with Chro&um Trioxide in Acetic -Acid .-The -method described previously for the oxidation of eso-2-chlorobicyclo[2.2.1] heptansyn-7-01 was employed.. A 0.119-g (0.657 mmol) sample of the dichloro alcohol in 2 ml of glacial acetic acid was treated with a solution of 0.064 g (0.64 mmol) of chromium trioxide in 6 ml of glacial acetic acid for 7 hr a t room temperature. After work-up there was obtained 0.116 g of a tan solid whose infrared spectrum showed no hydroxyl absorption, but did show carbonyl absorptions at 5.48 (m) and 5.62 (9) p , initially suggesting a 7-keto structure. Recrystallization of the crude product from hexane followed by vacuum sublimation gave 0.032 g (27.2%) of a white crystalline solid, mp 101.5-102.5", which is indicated to be 3,3-dichlorobicyclo [2.2.1]heptan-2-one. Repeated attempts to prepare an ethylene ketal by the method of Meinwald, Meinwald, and Bakera were unsuccessful. The infrared spectrum had absorptions at 5.48 (m) and 5.62 (s) p for the carbonyl group while the nmr spectrum (cc14, TMS internal standard) exhibited absorptions at T 6.94 (multiplet, 1, C4), 7.18 (multiplet, 1, Cl), and 7.4-8.5 (complex, 6). Hydrolysis of 3,3-Dichlorobicyclo [Z 2.11 heptan-ezo-2-01.-This compound was hydrolyzed according to the procedure described by Baird." A rnixture of 0.108 g (0.596 mmol) of 3,3-dichlorobicyclo[2.2.1] heptan-em-2-01, 0.238 g of lithium carbonate, and 10 ml of water was heated to reflux for 32 hr. After cooling, the reaction mixture was filtered, and the filtrate was extracted continuously with ether for 12 hr. The ether extract was dried and concentrated to give 0.060 g of a light yellow liquid residue. In addition to a strong liydroxyl absorption a t 3.00 p the infrared spectrum showed fairly strong absorption in the carbonyl region a t 5.74 CC. The crude product was taken up in ether and washed with 10 ml of 40% sodium bisulfite solution. After drying and removal of the ether under reduced pressure, 0.023 g of a viscous, yellowbrown liquid remained. Vacuum sublimation gave a white semisolid material, which was recrystallized from cyclohexane to give a low yield of l-chlorobicyclo[2.2.1]heptane-ezoB,s~-7diol (12) as a white crystalline solid, mp 170-192" (sealed capillary). The melting point of the diol varied somewhat upon exposure to the moist atmosphere. The infrared spectrum of this product was identical with that of the diol (mp 200-202') obtained by the lithium aluminum hydride reduction of 1chloro-ezo-2,syn-7-diacetoxybicyclo [2.2.1]heptane (15). Reaction of 2-Chlorobicyclo[2 2.11hept-2-ene ezo-Oxide with Anhydrous Acetic Acid..-A 6.97-g (0.0482 mol) sample of 2chlorobicyclo[2.2.1] hept-2-ene ezo-oxide in a Dry Ice cooled addition funnel was added dropwise with stirring to 75 ml of anhydrous acetic acid at room temperature. The temperature of the reaction mixture increased to 32.3" during the addition and then gradually decreased again. After stirring for a total of 18 hr, the reaction mixture was taken LIP in ether and cooled in an ice bath while the acetic acid was neutralized by the addition of a cold saturated sodium bicarbonate solution. The ether layer was separated, washed with water, and dried. Concentration mder reduced pressure gave 6.59 g of a light yellow liquid residue. Gc analysis of the crude product using a 0.25 in. X 6 ft 20Y0 Carbowax 20M on 60/80 Chromosorb W column at 200' showed the presence of fourteen major components besides some solvent. The retention times and integrated percentages were as follows: peak no. 1, 0.99 min, 0.77,; peak no. 2, 1.70 min, 1.77,; peak no. 3, 2.98 min, 2.7%; peak no. 4, 3.33 min, 3.0%; peak no. 5, 3.59 min, 0.6%; pe.sk no. 6, 3.88 min, 5.07,; peak no. 7, 4.56 min, 13.3%; peak no. 8, 4.95 min, 3.5%; peak no. 9, 6.09 min, 12.6%; peak no. 10, 6.90 min, 4.170; peak no. 11, 7.52 min, 8.9%; peak no. 12, 13.20 min, 5.570; peak no. 13, 14.66 min, 24.4%; and peak no. 14, 15.97 min, 14.0%. These integrated percentages are only approximate owing to the overlap of some of the peaks. Peak no. 2 was indicated to be unreacted epoxide by its retention time. Peaks no. 6 and 8 were identified as ezo- and endo-3chlorobicyclo[2.2.l] heptan-2-one, respectively, by comparison of retention times, and by collection of the components and cornparison of their infrared spectra with those of known samples. Peak no. 7 was identified as ezo-2-chlorobicyclo[2.2.1]heptan-7-
The Journal of Organic Chemistry one by its retention time and by the infrared spectrum of a collected sample. I n the same manner peak no. 11 was identified as 3,3-dichlorobicyclo[2.2.1] heptan-ezo-2-01. Peak no. 9 was heptan-7collected and identified as ezo-2-acetoxybicyclo[2.2.1] one by comparison of its infrared spectrum with that of an authentic sample.19 Collection of peak no. 13 from the gc gave a white crystalline solid, which after recrystallization from hexane melted at 70.771.7'. An osmometric molecular weight determination in ethanol gave a value of 196.8, suggesting the addition of a molecule of acetic acid to epoxide 2. The infrared spectrum exhibited absorptions at 3.03 ( s ) (0-H), 5.75 (9) and 8.12 p (9) (acetate). The nmr spectrum (CC4, TMS internal standard) exhibited absorptions at 7 5.14 (triplet, 1, endo-Cz), 6.17 (multiplet, 1, anti-C,), 7.45 [doublet (J = 4.5 cps), 1, hydroxyl], and 7.5-9.1 (multiplet, 10) with an intense singlet at 7 7.97 due to the methyl of the acetoxyl substituent. After treatment of the sample with deuterium oxide, the doublet at T 7.45 was gone and the multiplicity at 6.17 was simplified. From mechanistic [2.2 .l]considerations the structure 1-chloro-ezo-2-acetoxybicyclo heptan-syn-7-01 (14) is assigned. Anal. Calcd for CsH&lOa: C, 52.82; H, 6.40; mol wt, 204.66. Found: C, 52.57; H, 6.37. Collection of peak no. 14 from the gc also gave a white crystalline solid, which after recrystallization from hexane melted a t 92.5-93.0'. An osmometric molecular weight determination in ethanol gave a value of 250.7. The infrared spectrum contained absorptions a t 5.73 (6) and 8.00 p (s) for the acetates and the nmr spectrum (CC14,TMS internal standard) exhibited absorptions at 7 5.13 (complex, 2, endo-C* and anti-C,) and 7.5-8.8 (complex, 13, methyl absorptions at 7 7.96 and 8.00). These dat,a are in accord with the structure of l-chloro-ezo-2,syn-7diacetoxybicyclo I2.2.11heptane (15). Anal. Calcd for C11HlaClOa: C, 53.56; H, 6.13; mol wt, 246.69. Found: C, 53.85; H, 6.21. Owing to poor separation for collections, insufficient quantities of the remaining peaks (no. 1, 3, 4, 5, 10, and 12) could be obtained for identification. These six components account for a total of 16.670 of the products. N o further attempts were made to identify these peaks. Acetylation of 1-Chloro-ezo-2-acetoxybicyclo[2 2.11heptan-syn7-ol.-A mixture of 0.062 g (0.303 mmol) of l-chloro-ezo-2acetoxybicyclo[2.2.1] heptan-syn-7-01, 1 ml of pyridine, and 0.5 ml of acetic anhydride was allowed to stir at room temperature for several days. The mixture was then added to ca. 25 ml of water, and, while cooling in an ice bat,h, 10% hydrochloric acid was added dropwise until the pyridine odor had nearly disappeared. The resulting mixture was extracted with four 6-ml portions of pentane, and the combined pentane extracts were washed with two 10-ml portions of
